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Norman (“Ned”) Sharpless, MD, Nominated as Director of the National Cancer Institute
The AACR congratulates Ned Sharpless, MD, on his
nomination by President Donald Trump to serve as the 15th director of the
National Cancer Institute (NCI).
Sharpless brings impressive qualifications to this extremely important
position, including his background as a top-tier physician-scientist and his
previous positions at the University of North Carolina (UNC), including his
current role as director of the prestigious UNC Lineberger Comprehensive Cancer
Center," said AACR President Michael A. Caligiuri, MD, director, The Ohio
State University Comprehensive Cancer Center and chief executive officer of the
Arthur G. James Cancer Hospital and Richard J. Solove Research Institute. "His enthusiasm for innovative
scientific methods and ideas, as well as his appreciation for the value and
importance of basic research to advancing translational discoveries, will allow
the NCI to continue leading the way in programs aimed at preventing disease,
improving health and reducing suffering from cancer, while also helping to
maintain America’s edge in the life sciences."
Sharpless will succeed Doug Lowy, MD, who has served as acting director of the
NCI since the spring of 2015. During his
two years as acting director, Dr. Lowy provided critical leadership to advance
the National Cancer Moonshot Initiative that Vice President Biden spearheaded
during the final year of the Obama Administration.
“The entire cancer research and patient care
community owes Dr. Lowy a tremendous amount of gratitude over the past two
years for his extraordinary dedication and outstanding commitment to reducing
cancer incidence, morbidity, and mortality,” said Margaret Foti, PhD, MD (hc),
chief executive officer of the AACR. “Last night’s appointment by President
Trump to select Dr. Sharpless as NCI’s next director ensures a continuity in
leadership and management at the NCI that is especially needed during this
historic era of unprecedented scientific opportunities that are before us.
Therefore, we are absolutely thrilled about Dr. Sharpless’ appointment as we greatly
respect and value his expertise and leadership in the cancer research
community, and the AACR truly looks forward to working with Dr. Sharpless in
the months and years to come.”
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Basket Trials: Accelerating Precision Medicine
Benjamin Wolfson is a PhD Candidate in Molecular Medicine at the University of Maryland, Baltimore, focusing on the role of noncoding RNAs in the breast cancer microenvironment. Find more of his writing here and follow him on Twitter.
On May 23rd 2017, the cancer research community applauded a landmark accomplishment when for the first time the U.S. Food and Drug Administration (FDA) approved Merck's pembrolizumab for use in tumors located in any tissue. While cancers are traditionally organized and treated based on their tissue of origin, tumor sequencing has demonstrated that there are important genetic and molecular similarities between tumors across tissue types. These data prompted researchers to hypothesize that molecularly targeted therapies could be effective independent of a disease's tissue of origin or histology. This means that drugs that have been approved for one cancer type may be effective in others as well as long as the molecular target is present, leading to exciting new avenues of treatment across all cancers.
In the past, cancer drug approval in different diseases was accomplished by carrying out individual clinical trials for each tumor type. The FDA has approved almost 70 targeted therapeutic agents, many for use in multiple cancers, including trastuzumab (approved in both breast cancer and adenocarcinoma of the stomach) and imatinib (first approved in leukemia and later approved in four additional cancers). However, the traditional clinical trial paradigm is prohibitive to high-throughput drug development; standard clinical trials are designed to test the efficacy of one drug in one disease at a time, a process that can take between 5-10 years per tissue type.
While the same drug can be approved for different diseases through multiple, time consuming, iterations of this process, researchers are designing new, broader, clinical trial paradigms to speed up the approval of drugs in other diseases. One of the most exciting of these new methodologies is the basket trial, which allows clinicians to investigate multiple drugs or diseases under the same clinical trial framework, each in their own "basket." By analyzing a patient's tumor response in the context of their basket, the trial can fluidly evolve to match how patients respond; baskets that do not respond well can be discontinued, while those demonstrating a good drug response can be immediately expanded to test the drug in a larger group. If a drug is shown to be effective regardless of tumor location, it may be approved for use in drug-target containing tumors located in any tissue, even those not included in the basket trial (tissue-agnostic use).
The first cancer drug to garner FDA approval for tissue-agnostic use is pembrolizumab. Pembrolizumab was first approved for treatment of patients with melanoma, and later for use in lung and several other solid tumor cancers, each after an independent traditional clinical trial. To investigate pembrolizumab in additional tissue sites, Merck initiated a basket trial investigating pembrolizumab's efficacy in patients with 15 different cancer types, all expressing pembrolizumab's target, PD-1. Based on the positive results of these trials, the FDA granted pembrolizumab accelerated approval, meaning it will undergo further study but is immediately available to patients whose disease will progress without it. This tissue-agnostic drug approval has been met with tremendous enthusiasm from the cancer research community, and may be the next step toward delivering on the promise of personalized medicine. The advent of next generation sequencing has made it easier, cheaper, and faster to sequence a patient's tumor as a routine test when performing biopsies, and identification of a tumor's exact genetic landscape means that the most important mutations and targets can be identified. This allows doctors to create an individualized treatment regimen according to a patient's tumor-specific mutations, and the approval of drugs for tissue-agnostic use significantly increases the number of drugs available for targeted treatment.
Increased implementation of the basket trial design will benefit patients that are the underserved by classic clinical trials. Often it is difficult to recruit enough participants for clinical trials testing rare mutation-targeting drugs leaving patients with these mutations without effective treatment options. Basket trials can expand the population of patients eligible for a trial, benefiting those with less common diseases. Moreover, trials can be conducted in a shorter time, with fewer patients, and at lower cost than traditional trial designs.
Despite these benefits, basket trials do have disadvantages. First, the presence of a molecular target in a tumor does not guarantee it plays an important role or that inhibition of that target will have a beneficial effect for the patient. This was recently demonstrated with the BRAF inhibitor vemurafenib. While it is highly effective in BRAF mutation-carrying, metastatic, melanoma patients, it is ineffective in colorectal cancer with mutated BRAF. Basket trials also increase the statistical complexity of a clinical trial. Each basket of the trial carries its own chance of resulting in a false positive, which combine to increase the rate of false positives for the trial as a whole. Finally, it's nearly impossible to simplify tumors down to one or two targetable mutations. The biological context of mutations impacts the role that a mutation has in the tumor, and basket trials will only show that a treatment works if the tumor's survival relies on the targeted pathway.
We remain on the cusp of a true paradigm shift in personalized genomics and medicine, and the approval of pembrolizumab for tissue-agnostic use is the first glimpse of this future. Forty three percent of all tumors share more genetic similarities to tumors from different tissues than tumors from their own tissue of origin, and yet we still classify and treat cancers based on their tissue of origin. This is a rudimentary construct for what are incredibly complicated diseases. Basket trials are the first clinical reflection of the need to change this, and will set the foundation for more innovative clinical trial design to fulfill the hopes of personalized cancer treatment.
For more information concerning the approval of pembrolizumab, and to stay up to date with current events in cancer drug development and approval, we recommend the FDA's new podcast: Drug Information Soundcast in Clinical Oncology (D.I.S.C.O.)
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New Paper on Oncology Clinical Pathways Highlighted at Turning the Tide Conference
On Thursday, June 29, thought
leaders from across the cancer community gathered in the nation’s
capital to explore solutions that foster continued innovation and
deliver better outcomes for patients. Co-hosted by the Personalized
Medicine Coalition (PMC), the American Association for Cancer Research
(AACR), Feinstein Kean Healthcare (FKH), and CancerCare, the third national conference of the Turning the Tide Against Cancer Through Sustained Medical Innovation initiative
brought together stakeholders from the scientific, clinical,
regulatory, industry, and patient advocacy communities to participate in
solutions-oriented discussions that delineate strategies for
policymakers to consider that support meaningful patient engagement and
deliver value to patients.
The one-day program included interactive panels, spotlight sessions, and a keynote presentation by Joan Lunden, former host of Good Morning America,
journalist, author, patient advocate and breast cancer survivor, to
discuss value, innovation, and patient access and how these key areas of
concern render meaningful patient engagement more necessary in cancer
research and delivery of care.
“Regarding the critical issues of
clinical decision-making and reimbursement, the Turning the Tide
initiative reminds us again that the patient voice must be right front
and center in the cancer research and care process,” said Edward
Abrahams, PhD, president, PMC. “In order to realize the benefits of
personalized medicine — which represents the future of oncology — and
address the rising cost of cancer care, patients must be active
participants in treatment decision-making.”
Ahead of the fifth
anniversary of the Turning the Tide Against Cancer initiative, which
first convened in 2012, PMC, the AACR, and FKH convened an expert
working group of top leaders in cancer research, health care policy, and
patient advocacy to explore the shift from volume to value-based care
and how this may affect whether clinical pathways are effectively
facilitating patient access to high-quality and high-value care. Results
from the expert working group, published this week in the journal Clinical Cancer Research suggest
that a lack of accountability exists across the continuum of a pathway,
leading to the group’s recommendation that an independent third party
serve in an accreditation or oversight capacity for these tools. The
manuscript, Clinical Pathways: Recommendations for Putting Patients at the Center of Value-Based Care,
places the patient at the forefront of the discussion around cancer
care, a necessary concept and central theme of Turning the Tide.
is an amazing time in the field of oncology," said Margaret Foti, PhD,
MD (hc), chief executive officer of the AACR. "Scientific data is being
collected, shared, and utilized in more productive ways than ever
before, and cancer patients are finding it easier to search for and
enroll in a cancer clinical trial than at any time in our nation's
history. Discussions during today's conference will help catalyze a new
phase of community-wide action to ensure that cancer patients' voices
become an even more integral part of the cancer research and care
“We are positioned at a unique convergence in
health care, with the influx of scientific innovation, health data, and
patient engagement driving a shift to value-based care,” said Marcia
Kean, MBA, chairman, Strategic Initiatives, FKH. “It is our collective
responsibility to incorporate the patient perspective as we develop new
health care delivery models so that we can align patient priorities and
preferences with available scientific evidence to drive appropriate
At the Turning the Tide Against Cancer 2017
National Conference, experts working in oncology innovation and
healthcare policy gathered for a dialogue featuring a full patient panel
to open and close the event, and an extensive lineup of speakers dedicated to finding solutions that drive patient-centered care.
“It’s time for patient-centered care to be the standard of care,” said Patricia Goldsmith, chief executive officer, CancerCare.
“Progress toward this requires partnerships across industry, policy,
and advocacy to catalyze broad community action to ensure that the
patient’s voice is an integral part of the cancer research and care
system. Through the Turning the Tide Against Cancer 2017 National
Conference and in the coming years, we remain committed to fulfilling